ABSTRACT There is rapidly growing evidence that the health and development of the child and adult can be traced to early environmental influences. However, the vast majority of the evidence is correlational: fundamental questions remain about which specific early exposures confer risk, when in development exposure may have significant and lasting influence, and the mechanisms of effects. This application to the Environmental Influences on Child Health Outcomes (ECHO) RFA (OD-16-004) synthesizes two recently initiated and highly compatible pediatric cohort studies in which environmental exposures are being tracked in 500 pregnant mothers from the 1st trimester; we are already collecting extensive prenatal biological samples and placental samples as well as detailed psychological, socio-demographic, and life history data. We especially target the prenatal period to examine if and how prenatal exposures may ?program? adaptive biological responses in the fetus and child, with carry-forward effects on brain and somatic health; furthermore, we focus particularly on inflammation as a mediator of environmental exposures because it is a compelling biological mechanism by which a wide range of exposures may shape child neurodevelopment and obesity. These data, which cover cellular mechanisms and social demography, will help translate how the range of environmental influences from pregnancy shape child health outcomes. The 500 children will be extensively studied at newborn, 6 months, 1 year, 2 years, 3 years, and 4 years of age using clinically derived and state-of-the-art behavioral, physical and biological assessments of neurodevelopment and obesity. In the UG3 phase we will harmonize protocol development across sites; complete collection of prenatal and a substantial majority of placental samples and perinatal outcomes across cohorts; commence collection of neonatal brain imaging and physical development outcomes. We will also develop models for the biological and social and demographic exposure data in preparation for analyses of child health outcomes in the UH3 phase. For the UH3 phase, we will characterize inflammation from multiple sources throughout pregnancy, in the placenta, and in early infant development to identify its psychosocial, developmental, and environmental exposure origins and sources. In addition, we will test alternative mechanisms by which prenatal exposures and indicators of inflammation predict perinatal outcomes, child obesity, and child neurodevelopment. We will also complete the complex task of biobanking extensive blood, urine, saliva and place samples on approximately 1,000 individuals and contributing the broader ECHO consortium research agenda. The proposed study will add significant new information to our understanding of which environmental influences may have causal influence on child health outcomes, and the timing and mechanisms of these effects. This information will provide a much-needed empirical foundation to know how and when in development to intervene to promote child health outcomes.